Preface


Why cisplatin? Why would anyone write about the anticancer drug cisplatin? Why not some other, relatively recent drug such as taxol? Well, many reasons actually. Cisplatin has a long and interesting history, being first discovered as having anticancer properties in 1970 by accident. It is a very simple inorganic compound, and yet is one of the most effective and widely used antineoplastic in the world.

During my time spent researching this project, I have come to make a common observation. Casual communication with fellow chemists also studying an anticancer drug, such as taxol, have led me to believe that many, like most people, are not entirely aware of the fundamental facts behind cancer and chemotherapy. This presumably is due to a combination of ignorance, insufficient research and limited ability in understanding the biological texts. Having a conversation with someone who does not understand the very basic but fundamental facts of the subject is extremely infuriating. (It is hoped one has not made similar mistakes here!) An example of such facts, is the common misconception of the relative rates of cell division. Cancer cells do not divide any faster than normal, dividing non-cancerous cells, such as those that line the gastrointestinal tract. Only in a very few exceptional tumours, will rate of cell division be greater. The actual significant difference between a cancer cell and a normal cell, is with regulation. Cancer cells can and will divide in an uncontrolled manner whilst normal cells do not. It is perhaps the inaccurate interpretation of such a sentence that has led most people to believe that cancer cells divide at a much faster rate. When one says "uncontrolled", one literally means "unregulated", which although has the exact same meaning, seems not to... Cell division occurs at similar rates to that of normal cells, however, they can continue to divide indefinitely while normal cells cannot. Again, this is also open to misinterpretation. An indefinite phase of cell division simply implies continual cellular replication but at the same rate, not an increased rate. This fundamental fact is of great importance to that of cancer treatment. Anticancer drugs therefore, affect all actively dividing cells regardless of their type, be they cancerous or not. Although more obscure, this is yet another fundamental fact that is understandably, not fully realised. The significance of this which must be stressed, is that antineoplastics do not target cancer cells specifically. Selectivity is only observed for specific types of cancers which have deficient repair mechanisms, or some distinguishing feature such as a unique cell-surface receptor. In these few cases, drugs can be designed to target these cancer cells by identifying their specific "labels". One research group , are currently trying to specifically label the cancer cells, to allow for selective targeting by anticancer drugs. This, they have called "Fatal Engineering". Consequently, most anticancer agents are in general, totally indiscriminate and will thus affect normal dividing cells as well as cancer cells. Indeed, this is the primary cause of the numerous side effects associated with chemotherapeutic agents. Hair loss, nausea and anaemia are a few of the direct consequences of anticancer drug low selectivity. There is therefore, a fine balance between the number of cancer cells that can be killed for effective treatment, and the number of normal healthy cells that can be killed to allow for a full recovery. If anticancer drugs were actually selective as some people may think, cancer would not be such a wide disease of the world as it is today. Patients would not dread the side effects associated with them, as there would not be any. Note, that an anticancer agent able to selectively target cancer cells specifically would in fact, be the cure to the disease itself!

One of the intended aims of this project is to inform and make aware of these facts to the general public. It will try to deliver biological knowledge in a more easily accessible way. As the general audience will consist primarily of chemists, I have tried to keep the language simple. However, as I have ensured that the following information is accurate, it is recommended that readers have some prior biological knowledge. Those who do not are warned that the following pages may not be an easy read. Of the original title A brief treatment of cisplatin and their analogues, the "brief" had to be removed after further research and comparison with other projects. With a personal interest in cancer research and treatment, I do not consider this piece to be lengthy, however, most readers would probably think otherwise.

It must be noted, that unfortunately not all the electronic references used for this project are present in the references page. This was simply because some of the URLs were not recorded during preliminary reseach, while some were lost after a few system failures.

I would like to give special appreciation to Mr W.M. Liu and the Barry Reed Oncology Department at Saint Bartholemew's Hospital for providing information and the use of their resources.

 

Imperial College, 1998 S.M. Liu

Introduction

Copyright 1998 Sai Man Liu

All Rights Reserved.

Last Modified on 24 June 1998